X-13734776-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003611.3(OFD1):c.-296G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,056,115 control chromosomes in the GnomAD database, including 26,388 homozygotes. There are 86,786 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (3264 hom., 9650 hem., cov: 24)
  • Exomes 𝑓: 0.26 (23124 hom. 77136 hem.)
• Consequence: OFD1 NM_003611.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83

Genes affected

OFD1 (HGNC:2567): (OFD1 centriole and centriolar satellite protein) This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Many pseudogenes have been identified; a single pseudogene is found on chromosome 5 while as many as fifteen have been found on the Y chromosome. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant X-13734776-G-T is Benign according to our data. Variant chrX-13734776-G-T is described in ClinVar as [Benign]. Clinvar id is 41157.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OFD1	NM_003611.3	c.-296G>T		5_prime_UTR_variant	1/23	ENST00000340096.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OFD1	ENST00000340096.11	c.-296G>T		5_prime_UTR_variant	1/23	1	NM_003611.3	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 31241 AN: 111742 Hom.: 3257 Cov.: 24 AF XY: 0.284 AC XY: 9628 AN XY: 33942

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.260 AC: 245282 AN: 944320 Hom.: 23124 Cov.: 30 AF XY: 0.265 AC XY: 77136 AN XY: 290982

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.280 AC: 31267 AN: 111795 Hom.: 3264 Cov.: 24 AF XY: 0.284 AC XY: 9650 AN XY: 34005

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.297

Alfa AF: 0.248 Hom.: 15281

Bravo AF: 0.302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.10
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2285635; hg19: chrX-13752895;